Perampanel (FYCOMPA™) is a first-in-class, highly selective non-competitive AMPA-type glutamate receptor antagonist indicated for adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older. Perampanel is chemically designated 5′-(2-cyanophenyl)-1′-phenyl-2,3′-bipyridinyl-6′(1′H)-one or 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one, and is represented by the following chemical structure:

Perampanel and other 1,2-dihydropyridine compounds which possess antagonistic action against AMPA receptor and/or inhibitory action against kainate receptor are described in WO 01/96308. Example 7 in WO 01/96308 discloses a process for producing perampanel by reacting 3-(2-cyanophenyl)-5-(2-pyridyl)-2(1H)-pyridone with phenyl boronic acid, copper acetate and triethylamine in methylene chloride, followed by addition of concentrated aqueous ammonia, water and ethyl acetate. After work-up (phase separation, washing the organic phase and drying over magnesium sulfate), the solvent was concentrated in vacuo and the residue was purified by a silica gel column chromatography (ethyl acetate:hexane=1:2) to give the title product as pale yellow powder. There is no disclosure regarding the polymorphic nature of the product.
A new crystalline or amorphous form of a compound may possess physical properties that differ from, and are advantageous over, those of other crystalline or amorphous forms. These include, packing properties such as molar volume, density and hygroscopicity; thermodynamic properties such as melting temperature, vapor pressure and solubility; kinetic properties such as dissolution rate and stability under various storage conditions; surface properties such as surface area, wettability, interfacial tension and shape; mechanical properties such as hardness, tensile strength, compactibility, handling, flow and blend; and filtration properties. Variations in any one of these properties may affect the chemical and pharmaceutical processing of a compound as well as its bioavailability and may often render the new form advantageous for pharmaceutical and medical use.
EP 1764361 (US 2010/324297) discloses three anhydrous crystalline forms of perampanel, designated Form I, Form III and Form V and a hydrate form of perampanel. Anhydrous Form I is prepared in accordance with Example Dl by dissolving perampanel in ethyl acetate (EtOAc) under reflux, cooling the solution, seeding with anhydrous perampanel crystals, continued cooling and collecting the precipitated crystals. Anhydrous Form V is prepared in accordance with Example C1, by dissolving perampanel in acetone, heating to reflux and concentrating the solution to solidification, dissolving the solids in acetone-water, refluxing then cooling and collecting the precipitate. The hydrate form is prepared in accordance with Example B1 by dissolving perampanel in acetone-water, heating, cooling the solution, seeding with perampanel hydrate crystals, continued cooling and collecting the precipitated crystals.
US 2009/0088574 discloses a crystalline form of perampanel designated Form IV, which is prepared by slurring perampanel in an acetone/water mixture.
U.S. Pat. No. 7,803,818 discloses an amorphous form of perampanel which is prepared by spray drying perampanel from an acetone solution.
U.S. Pat. No. 7,718,807 discloses acid addition salts of perampanel or a hydrate thereof, wherein the acid is selected from the group consisting of benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, fumaric acid, tartaric acid, succinic acid and benzoic acid.
There still remains an unmet need for solid state forms of perampanel having good physicochemical properties, desirable bioavailability, and advantageous pharmaceutical parameters.